Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.

Gastric cancer (GC) is a highly aggressive malignancy with limited treatment options for advanced-stage patients. Recent studies have highlighted the role of circular RNA (circRNA) as a novel regulator of cancer progression in various malignancies. However, the underlying mechanisms by which circRNA contributes to the development and progression of GC remain poorly understood. In this study, we utilized microarrays and real-time quantitative polymerase chain reaction (qRT-PCR) to identify and validate a downregulated circRNA, hsa_circ_0003251 (referred to as circWNK1), in paired GC and normal tissues. Through a series of in vitro and in vivo gain-of-function and loss-of-function assays, we demonstrated that circWNK1 exerts inhibitory effects on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. Additionally, we discovered that circWNK1 acts as a competitive endogenous RNA (ceRNA) for SMAD7 by sequestering miR-21-3p. Our findings were supported by comprehensive biological information analysis, as well as RNA pull-down, luciferase reporter gene, and western blot assays. Notably, the downregulation of circWNK1 in GC cells resulted in reduced SMAD7 expression, subsequently activating the TGF-ß signaling pathway. Collectively, our study reveals that circWNK1 functions as a tumor suppressor in GC by regulating the miR-21-3p/SMAD7-mediated TGF-ß signaling pathway. Furthermore, circWNK1 holds promise as a potential biomarker for the diagnosis and treatment of GC.

A prediction nomogram for hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: The present study aimed to develop and validate a new nomogram for predicting the incidence of hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients receiving antiviral therapy from real-world data. METHODS: The nomogram was established based on a real-world retrospective study of 764 patients with HBV from October 2008 to July 2020. A predictive model for the incidence of HCC was developed by multivariable Cox regression, and a nomogram was constructed. The predictive accuracy and discriminative ability of the nomogram were assessed by the concordance index (C-index), calibration curves, and decision curve analysis (DCA). Risk group stratification was performed to assess the predictive capacity of the nomogram. The nomogram was compared to three current commonly used predictive models. RESULTS: A total of 764 patients with HBV were recruited for this study. Age, family history of HCC, alcohol consumption, and Aspartate aminotransferase-to-Platelet Ratio Index (APRI) were all independent risk predictors of HCC in CHB patients. The constructed nomogram had good discrimination with a C-index of 0.811. The calibration curve and DCA also proved the reliability and accuracy of the nomogram. Three risk groups (low, moderate, and high) with significantly different prognoses were identified (p < 0.001). The model's performance was significantly better than that of other risk models. CONCLUSIONS: The nomogram was superior in predicting HCC risk among CHB patients who received antiviral treatment. The model can be utilized in clinical practice to aid decision-making on the strategy of long-term HCC surveillance, especially for moderate- and high-risk patients.

Construction of a miRNA-mRNA network related to exosomes in metastatic hepatocellular carcinoma.

Aims: This study aimed to construct a miRNA-mRNA network to elucidate the molecular mechanism of exosome function in metastatic HCC. Methods: We explored the Gene Expression Omnibus (GEO) database and then analyzed the RNAs of 50 samples to obtain differentially expressed miRNAs (DEMs) and mRNAs (DEGs) involved in the progression of metastatic HCC. Next, a miRNA-mRNA network related to exosomes in metastatic HCC was constructed on the basis of the identified DEMs and DEGs. Finally, the function of the miRNA-mRNA network was explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Immunohistochemistry was performed to validate expression of NUCKS1 in HCC specimens. Based on the immunohistochemistry, the score of the NUCKS1 expression was calculated, and the patients were divided into high- and low-expression patients, and the differences in survival between the two groups were compared. Results: Through our analysis, 149 DEMs and 60 DEGs were identified. In addition, a miRNA-mRNA network, including 23 miRNAs and 14 mRNAs, was constructed. Low expression of NUCKS1 was validated in the majority of HCCs compared with their matched adjacent cirrhosis specimens (P < 0.001), which was consistent with our result of differential expression analyses. HCC patients with low expression of NUCKS1 had shorter overall survival than those with high NUCKS1 expression (P = 0.0441). Conclusions: The novel miRNA-mRNA network will provide new insights into the underlying molecular mechanisms of exosomes in metastatic HCC. NUCKS1 might serve a potential therapeutic target to restrain the development of HCC.

A Maximization of the Proton Conductivity of Sulfonated Poly(Ether Ether Ketone) with Grafted Segments Containing Multiple, Flexible Propanesulfonic Acid Groups.

To enhance the proton conductivity of sulfonated poly(ether ether ketone) (SPEEK), proton-conducting groups are required to be covalently connected to SPEEK and form proton-conducting channels. Herein, SPEEK fully grafted with segments containing multiple, flexible propanesulfonic acid groups (MS-SPEEK-102) is successfully prepared. Compared with SPEEK, MS-SPEEK-102 exhibits a higher proton conductivity of 8.3 × 10-2  S cm-1 at 80 °C with 98% relative humidity, and consequently a greater power density of 0.530 W cm-2 at 60 °C. These can be ascribed to the increased number of sulfonic acid groups, and ample, uninterrupted proton-conducting channels constructed by the movement of the maximum content, flexible side-chain segments. This approach offers an idea for obtaining a proton exchange membrane with good proton conductivity based on SPEEK.

Alterations of monoamine neurotransmitters, HPA-axis hormones, and inflammation cytokines in reserpine-induced hyperalgesia and depression comorbidity rat model.

BACKGROUND: Pain and depression often occur simultaneously, but the mechanism of this condition is still unclear. METHODS: The aim of this study was to examine the alterations of monoamine neurotransmitters, hypothalamic-pituitary-adrenal (HPA) axis hormones, and inflammation cytokines in hyperalgesia and depression comorbidities. The reserpine-induced "Sprague Dawley" (SD) rat models were used, and the concentrations of monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE), dopamine (DA), and their metabolic products 5-hydroxyindoleacetic acid (5-HIAA), Homovanillic acid (HVA), 3,4-Dihydroxyphenylacetic acid (DOPAC) in raphe nucleus region were tested by High Performance Liquid Chromatography (HPLC). Serum levels of Adrenocorticotropic Hormone (ACTH), Cortisol (CORT), and inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, IL-10 were assessed by enzyme linked immunosorbent assay. RESULTS: Repeated reserpine injection induced hyperalgesia and depressive behaviors with decreased sucrose preference and horizontal movement distance, and increased immobility time in forced swimming test. The concentrations of 5-HT and NE in raphe nucleus, and ACTH and CORT in serum were elevated in the model group. And the model group showed increases in serum IL-1ß and IL-6, and decrease in serum IL-10. CONCLUSION: More research in these areas is needed to understand the pathogenesis of the disease, so as to find more and better therapeutic targets.

Identification and Validation of Hub Genes with Poor Prognosis in Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.

Background: Hepatocellular carcinoma (HCC) is the reason for the world's second largest cancer-related death. It is clinically valuable to study the molecular mechanisms of HCC occurrence and development for formulating more effective diagnosis and treatment strategies. Methods: The five microarray data sets GSE45267, GSE101685, GSE84402, GSE62232 and GSE45267 were downloaded from Gene Expression Omnibus (GEO) database, including 165 HCC tissues and 73 normal tissues. Differential expressed genes (DEGs) between HCC tissues and normal tissues were determined by GEO2R. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the protein-protein interaction network (PPI) network analysis were employed to identify DEGs and to evaluate the clinical significance in prognosis of HCC. Results: A total of 152 genes differentially expressed in HCC tissues and normal tissues were identified. GO and KEGG functional enrichment analysis revealed that 39 up-regulated genes were mainly enriched in mitosis, cell cycle and oocyte meiosis, while those down-regulated genes (113) were concentrated in exogenous drug catabolism and the metabolism of cytochrome P450 on exogenous drugs. Totally, 19 hub genes were chosen by PPI network and module analysis and verified by The Cancer Genome Atlas (TCGA) database. Finally, 8 hub genes were selected, including CDK1, CYP2C8, CCNB1, AURKA, CYP2C9, BUB1B, MAD2L1 and TTK, which were associated with the overall survival rate of HCC patients. Conclusion: This study presented eight target genes connected to the prognosis of HCC patients. Those mainly exists in cell cycle and drug catabolism, which may be latent targets for clinical treatment.

Icaritin Inhibits Migration and Invasion of Human Ovarian Cancer Cells via the Akt/mTOR Signaling Pathway.

Ovarian cancer (OC) is the most lethal of all gynecologic malignancies with poor survival rates. Although surgical treatment and chemotherapy had advanced to improve survival, platinum-based chemoresistance remains a major hurdle in the clinical treatment of OC. The search for novel active ingredients for the treatment of drug-resistant OC is urgently needed. Here, we demonstrated that icaritin, the main active ingredient derived from the traditional Chinese herb Epimedium genus, significantly suppressed the proliferation, migration, and invasion of both drug-susceptible and cisplatin-resistant OC cells in vitro. Mechanistically, icaritin at 20 µM significantly inhibited the phosphorylation of Akt and mTOR, as well as decreased the expression of vimentin and increased the expression of E-cadherin. Our data indicate that icaritin, a prenylated flavonoid natural product, could serve as a potential inhibitor of cisplatin-resistant OC by inhibiting the Akt/mTOR signaling pathway.

Two new photoactive metal-organic compounds for degradation of methylene blue and treatment in ophthalmic local anesthesia.

Two new metal-organic compounds, namely [Cu(CrO4)(4,4'-bipy)(H2O)]·n(H2O) (1) together with [Mn(Cr2O7)(bpp)2]n (2) (4,4'-bipy is 4,4'-bipyridine and bpp is 1,3-bis(4-pyridyl)propane), were hydrothermally generated, which were characterized structurally through a series of characterization techniques. Moreover, compounds 1 and 2 have 2.95 eV and 3.02 eV of narrow optical band gap values, and possess outstanding photocatalytic effects for the methylene blue degradation under irradiation of visible light. The application of above compounds in the ophthalmic local anesthesia was examined and the specific mechanism was tested. First of all, the acetylcholine content in the synaptic cleft was measured with enzyme linked immunosorbent assay (ELISA) assay after treated with the CPs. The acetylcholine receptor relative expression on nerve cells was subsequently measured via real time reverse transcription-polymerase chain reaction (RT-PCR) under the treatment of compounds. In the end, the complexes' toxicity was evaluated by Cell Counting Kit-8 (CCK-8) detection.

Liver abscess after microwave ablation of hepatocellular carcinoma caused by Clostridium perfringens.

Clostridium perfringens causes pyogenic liver abscesses, which are rare but rapidly fatal infections. These abscesses often occur in patients with immunodeficiency due to malignancy, liver cirrhosis, diabetes mellitus, or organ transplantation. The identification of gram-positive bacilli in septicemia, the presence of gas-forming liver damage and intravascular hemolysis are manifestations of Clostridium perfringens infection. Clostridioides toxin A hydrolyzes phospholipids in erythrocyte membranes, causing spherocytosis and subsequent intravascular hemolysis, resulting in rapid deterioration and a high mortality rate. A 62-year-old man with recurrent hepatocellular carcinoma complained of a high fever and abdominal pain one day after microwave ablation. Abdominal computed tomography revealed gas-containing lesions in the liver. His condition was complicated with massive hemolysis. Laboratory examinations revealed low hemoglobin, high serum lactate dehydrogenase, and elevated indirect bilirubin levels, suggesting massive intravascular hemolysis. Although aggressive treatment was applied, he died within 16 hours after onset of the infection. After the patient died, a blood culture indicated Clostridium perfringens positivity. Clostridium perfringens-induced septicemia with massive hemolysis is rare but rapidly leads to a severe prognosis. It is important to identify Clostridium perfringens infection early and initiate effective treatment, especially abscess aspiration, which should be performed as soon as possible.

Radial transport difference mediated by root endodermal barriers contributes to differential cadmium accumulation between japonica and indica subspecies of rice (Oryza sativa L.).

Although Cd concentration of grains is generally lower in japonica than in indica subspecies, the effects of root endodermal barriers on the subspecific differences in Cd accumulation in rice (Oryza sativa L.) are poorly understood. Here, we characterized the differences in endodermal differentiation between japonica and indica subspecies and their effects on Cd radial transport. Casparian strips (CSs) and suberin lamellae (SL) in japonica subspecies were initiated at the 6%- 7% and 21%- 27% position from the root tip, respectively, which were 65% and 26% earlier than in indica subspecies, respectively. The lignin/suberin content in japonica subspecies was 47%/42% greater than that in indica subspecies because of the higher expression of lignin/suberin biosynthesis-related genes (OsCASP1, OsPAL, OsCYP86A1 and OsKCS20). Cd exposure induced endodermal plasticity in both subspecies, but the changes in japonica were greater than in indica subspecies. The earlier formation of CSs/SL in japonica subspecies significantly restricted the flow of radial transport tracer to reach the xylem and decreased Cd influx into roots, that is, endodermal barriers inhibited Cd radial transport via both apoplastic and cell-to-cell pathways, thus decreasing the root-to-shoot transport of Cd in japonica subspecies. Our findings are beneficial for the genetic modification of rice with low-Cd-accumulating ability.

Factors affecting cadmium accumulation in the soil profiles in an urban agricultural area.

Soil Cd pollution is a serious environmental issue associated with human activities. However, the factors determining exogenous Cd dynamics in the soil profile in a complex environment are not well understood. Based on regional observations from 169 soil profiles across the Chengdu Plain, this study explored the key factors controlling Cd accumulation in the soil profile under actual field conditions. Results showed that total soil Cd contents decreased from 0.377 to 0.196 mg kg-1 with increasing soil depth. The effects of phosphate fertilizer rates, road density and precipitation on the difference in total soil Cd content were only observed in topsoil, while agricultural land-use type and topography had no impact. In contrast, significant differences in the total soil Cd content among different parent material types were found in the 0-20, 40-60 and 60-100 cm soil depths. One sample t-tests showed that significant Cd accumulation occurred in the whole soil profile in soils formed from Q4 (Quaternary Holocene) grey alluvium, while soils formed from Q3 (Quaternary Pleistocene) old alluvium and Q4 grey-brown alluvium showed significant Cd accumulation only in the 0-40 cm soil layers. In the topsoil, acid soluble Cd accounted for the largest proportion of the total Cd in soils formed from Q4 grey alluvium, reducible Cd was the main fraction in soils formed from Q4 grey-brown alluvium, while reducible Cd and residual Cd contributed the largest proportion of the total soil Cd in soils formed from Q3 old alluvium. The above results indicated that parent material was the decisive factor determining the magnitudes and depths of exogenous Cd accumulation in the soil profile due to its impacts on the Cd fraction distributions. These findings suggested that the parent material-induced Cd fraction distributions and accumulation should be considered for effectively exploring targeted remediation strategies for Cd pollution.

Effects of preoperative nasal spray esketamine on separation anxiety and emergence agitation in pediatric strabismus surgery: A randomized clinical trial.

OBJECTIVE: To investigate the effects of preoperative nasal spray esketamine on separation anxiety and postoperative emergence agitation in pediatric strabismus surgery. METHOD: Ninety children aged 3 to 6 years who underwent elective strabismus surgery were randomly divided into 3 groups that received 0.5 mg/kg (group S1), 1 mg/kg of esketamine (group S2), and the same volume of normal saline (group C) by nasal spray 10 minutes before surgery. The observation indicators of this test include the Ramsay sedation score, separation anxiety score, mask induction score, and the incidences of postoperative emergence agitation. Patient's heart rate, blood oxygen, post anesthesia care unit stay time, and any adverse events were recorded. RESULTS: The Ramsay sedation score was significantly lower in group C than those in groups S1 and S2 (P < .001). The separation anxiety scores and the mask induction scores were significantly higher in group C than those in groups S1 and S2 (P < .001). The incidences of emergence agitation in groups S1 and S2 were significantly lower than that in C group (P < .001). No obvious clinical complication was observed. CONCLUSION: Preoperative nasal spray esketamine reduced the preoperative separation anxiety and decrease emergence agitation in pediatric strabismus surgery.

Nomogram to predict overall survival based on the log odds of positive lymph nodes for patients with endometrial carcinosarcoma after surgery.

PURPOSE: Aims to compare the prognostic performance of the number of positive lymph nodes (PLNN), lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) and establish a prognostic nomogram to predict overall survival (OS) rate for patients with endometrial carcinosarcoma (ECS). METHODS: Patients were retrospectively obtained from Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015. The prognostic value of PLNN, LNR and LODDS were assessed. A prediction model for OS was established based on univariate and multivariate analysis of clinical and demographic characteristics of ECS patients. The clinical practical usefulness of the prediction model was valued by decision curve analysis (DCA) through quantifying its net benefits. RESULTS: The OS prediction accuracy of LODDS for ECS is better than that of PLNN and LNR. Five factors, age, tumor size, 2009 FIGO, LODDS and peritoneal cytology, were independent prognostic factors of OS. The C-index of the nomogram was 0.743 in the training cohort. The AUCs were 0.740, 0.682 and 0.660 for predicting 1-, 3- and 5-year OS, respectively. The calibration plots and DCA showed good clinical applicability of the nomogram, which is better than 2009 FIGO staging system. These results were verified in the validation cohort. A risk classification system was built that could classify ECS patients into three risk groups. The Kaplan-Meier curves showed that OS in the different groups was accurately differentiated by the risk classification system and performed much better than FIGO 2009. CONCLUSION: Our results indicated that LODDS was an independent prognostic indicator for ECS patients, with better predictive efficiency than PLNN and LNR. A novel prognostic nomogram for predicting the OS rate of ECS patients was established based on the population in the SEER database. Our nomogram based on LODDS has a more accurate and convenient value for predicting the OS of ECS patients than the FIGO staging system alone.

Knockdown of PYCR1 suppressed the malignant phenotype of human hepatocellular carcinoma cells via inhibiting the AKT pathway activation.

Hepatocellular carcinoma (HCC) is a common and highly malignancy tumor. Pyrroline-5-carpoxylate reductase-1 (PYCR1) is an active enzyme involved in cell metabolism. In this study, we explored the role of PYCR1 in the HCC cell lines, Hep3B and HepG2. The expression of PYCR1 was up-regulated in liver hepatocellular carcinoma (LIHC) tissue by GEPIA. Meanwhile the overall survival rate (OS) showed that patients with high PYCR1 expression had a worse prognosis compared with patients with low PYCR1 level. In addition, knockdown of PYCR1 suppressed the proliferation, invasion and migration of Hep3B and HepG2 cells and promoted the apoptosis and G1 arrest. Knockdown of PYCR1 reduced the expression of the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax and Caspase3. Furthermore, knockdown of PYCR1 changed the expression of p-AKT and its target gene Cyclin D1. In conclusion, knockdown of PYCR1 inhibited the malignant phenotype of human HCC cells by regulating the AKT pathway activation, which provides a potential strategy for the human HCC therapy.

Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients.

Chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC) is a major health problem in Asian-Pacific regions. Antiviral therapy reduces, but does not completely prevent, HCC development. Thus, there is a need for accurate risk prediction to assist prognostication and decisions on the need for antiviral therapy and HCC surveillance. A few risk scores have been developed to predict the occurrence of HCC in CHB patients. Initially, the scores were derived from untreated CHB patients. With the development and extensive clinical application of nucleos(t)ide analog(s) (NA), the number of risk scores based on treated CHB patients has increased gradually. The components included in risk scores may be categorized into host factors and hepatitis B virus factors. Hepatitis activities, hepatitis B virus factors, and even liver fibrosis or cirrhosis are relatively controlled by antiviral therapy. Therefore, variables that are more dynamic during antiviral therapy have since been included in risk scores. However, host factors are more difficult to modify. Most existing scores derived from Asian populations have been confirmed to be accurate in predicting HCC development in CHB patients from Asia, while these scores have not offered excellent predictability in Caucasian patients. These findings support that more relevant variables should be considered to provide individualized predictions that are easily applied to CHB patients of different ethnicities. CHB patients should receive different intensities of HCC surveillance according to their risk category.

CAP2 contributes to tumorigenesis in gastric cancer by targeting transcription factor SOX9.

BACKGROUND: Gastric cancer (GC) is one of the most common tumors and the major cause of cancer-related mortality in the world. The purpose of this study is to identify new biomarker and reveal its potential molecular mechanism in GC. METHODS: The expression of CAP2 was observed by the bioinformatics analysis and western blot assays. The effects of CAP2 on cell proliferation and growth were tested by MTT assay, EdU assay, colony formation assay, and flow cytometric assay, respectively. ChIP and dual-luciferase assays were confirmed that SOX9 binding sites were putative regulatory elements in the transcriptional activation of CAP2. Furthermore, western blot and xenograft assays were applied to examine whether SOX9 was involved in the regulation of CAP2 expression. RESULTS: We reported that CAP2 is overexpressed in GC cells and tissues and related to a poorer prognosis for GC patients. Moreover, we found that knockdown of CAP2 suppressed the proliferation, growth, and cell cycle of GC cells. Besides, the transcription factor SOX9 participated in the CAP2-mediated proliferation of GC cells in vitro and in vivo. CONCLUSIONS: Our results provide novel evidence that CAP2 plays an essential role in the genesis and development of GC, thus potentially highlighting this gene as a therapeutic target.

MiR-216b regulates the tumorigenesis of gastric cancer by targeting PXN.

BACKGROUND: Accumulating evidence has demonstrated that microRNAs (miRNAs) are associated with tumorigenesis. miR-216b can play a vital role in the genesis and development of gastric cancer (GC), and its molecular mechanisms require further elucidation. METHODS: The biological effects of miR-216b in GC cells were investigated by MTT, transwell assays, and cell cycle. Western blot and luciferase assay were performed to demonstrate the direct binding of miR-216b on PXN 3'UTR. Furthermore, MTT, colony formation assays, transwell assays, and flow cytometry analysis, as well as xenograft mice model, were used to measure the effects of miR-216b-PXN on GC cell proliferation, migration, and invasion indicated by in vitro and in vivo. RESULTS: Our results showed that miR-216b acted as a tumor suppressor in GC progression. miR-216b overexpression suppressed GC cell proliferation, migration, and invasion in vitro. Luciferase reporter assays identified paxillin (PXN) as a novel target gene of miR-216b. PXN overexpression could partially rescue miR-216b-induced the inhibitory effects in GC cells. Besides, overexpression of miR-216b contributed to the activation of PI3K/AKT signaling via partly regulating PXN in GC cells. CONCLUSIONS: The above results showed that miR-216b could offer a novel therapeutic avenue by targeting PXN in GC.

The impact of topical lidocaine and timing of LMA removal on the incidence of airway events during the recovery period in children: a randomized controlled trial.

BACKGROUND: The timing of laryngeal mask airway (LMA) removal remains undefined. This study aimed to assess the optimal timing for LMA removal and whether topical anesthesia with lidocaine could reduce airway adverse events. METHODS: This randomized controlled trial assessed one-to-six-year-old children with ASA I-II scheduled for squint correction surgery under general anesthesia. The children were randomized into the LA (lidocaine cream smeared to the cuff of the LMA before insertion, with mask removal in the awake state), LD (lidocaine application and LMA removal under deep anesthesia), NLA (hydrosoluble lubricant application and LMA removal in the awake state) and NLD (hydrosoluble lubricant application and LMA removal in deep anesthesia) groups. The primary endpoint was a composite of irritating cough, laryngeal spasm, SpO2 < 96%, and glossocoma in the recovery period in the PACU. The secondary endpoints included the incidence of pharyngalgia and hoarseness within 24 h after the operation, duration of PACU stay, and incidence of agitation in the recovery period. The assessor was unblinded. RESULTS: Each group included 98 children. The overall incidence of adverse airway events was significantly lower in the LA group (9.4%) compared with the LD (23.7%), NLA (32.6%), and NLD (28.7%) groups (P=0.001). Cough and laryngeal spasm rates were significantly higher in the NLA group (20.0 and 9.5%, respectively) than the LA (5.2 and 0%, respectively), LD (4.1 and 1.0%, respectively), and NLD (9.6 and 2.1%, respectively) groups (P=0.001). Glossocoma incidence was significantly lower in the LA and NLA groups (0%) than in the LD (19.6%) and NLD (20.2%) groups (P< 0.001). At 24 h post-operation, pharyngalgia incidence was significantly higher in the NLA group (15.8%) than the LA (3.1%), LD (1.0%), and NLD (3.2%) groups (P< 0.001). CONCLUSIONS: LMA removal in the awake state after topical lidocaine anesthesia reduces the incidence of postoperative airway events. TRIAL REGISTRATION: ChiCTR, ChiCTR-IPR-17012347 . Registered August 12, 2017.

Identification of a six-gene signature associated with tumor mutation burden for predicting prognosis in patients with invasive breast carcinoma.

BACKGROUND: Breast cancer (BC) is one of the most common cancers with high mortality worldwide. In the present study, through bioinformatics analysis, we aimed to identify new biomarkers to predict the survival rate of BC patients. METHODS: Differentially expressed genes (DEGs) between low- and high-tumor mutation burden (TMB) groups were identified by using The Cancer Genome Atlas (TCGA) dataset and integrated analysis. Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the protein-protein interaction (PPI) network, were applied to predict the function of these above DEGs. Then, the Cox proportional hazard model was developed to screen DEGs. Based on the prognostic signature, survival analysis was used on The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) dataset. Finally, the single-sample gene set enrichment (ssGSEA) analysis was employed to estimate immune cells related to this signature. RESULTS: To create a prognostic signature, 6 DEGs were identified. The results revealed that the survival time of patients with high-risk scores based on the expression of the six-gene signature was dramatically shorter than that of patients with low-risk scores in BC. Furthermore, survival analysis and multivariate cox analysis indicated that the six-gene signature was an independent prognostic factor of BC. Then, we built a nomogram that integrated the clinicopathological factors with the six-gene signature to predict the survival probability of BC patients. We eventually predicted the 20 most vital small molecule drugs by CMap, and Nadolol was considered as the most promising small molecule to treat BC. Moreover, ssGSEA analysis showed that the 6 genes were closely associated with immune cells. CONCLUSIONS: We constructed a six-gene signature associated with TMB that can improve the prognosis prediction and could be seen as a biomarker for BC patients.

Antiviral therapy and hepatocellular carcinoma risk in hepatitis B patients with cirrhosis.

OBJECTIVES: Our goal was to evaluate the effect of antiviral therapy on hepatocellular carcinoma incidence for cirrhotic patients with lower hepatitis B virus DNA levels. METHODS: Consecutive cirrhosis patients from a US cohort (n = 381) and 408 patients from a Taiwan cohort were enrolled. Patients were classified into a low (<20 IU/ml) and high hepatitis B virus DNA group (≥20 IU/ml), and each was further stratified into treated and untreated subgroups. RESULTS: Except for hepatitis B e antigen, baseline characteristics were similar for both hepatitis B virus DNA groups. Antiviral therapy significantly reduced hepatocellular carcinoma incidence in cirrhotic patients with hepatitis B virus DNA ≥20 IU/ml at 5-years (12.2% vs. 22.8%) and 10-years (23.3% vs. 37.2%) (P = 0.0018). For cirrhotic patients with hepatitis B virus DNA <20 IU/ml, there was no statistically significant difference in cumulative hepatocellular carcinoma incidence between the treated and untreated groups. After adjusting for age, sex, and hepatitis B e antigen status, antiviral therapy was an independent predictor (hazard ratio 0.43, P < 0.0001) for reduced hepatocellular carcinoma risk in patients with hepatitis B virus DNA ≥20 IU/ml. CONCLUSION: Antiviral therapy was associated with a 57% reduction in hepatocellular carcinoma incidence in chronic hepatitis B patients with cirrhosis and hepatitis B virus DNA as low as 20 IU/ml (but no lower). However, hepatocellular carcinoma incidence remained substantial, regardless of hepatitis B virus DNA levels and treatment status, highlighting the need for ongoing hepatocellular carcinoma surveillance for all cirrhotic hepatitis B virus patients.